Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Hemorrhagic cystitis (HC) is a relatively rare bladder disease with a complex etiology. With the growing number of patients with pelvic radiation therapy, incidence of this disease has risen considerably. Although treatments like hyperbaric oxygen (HBO) had some benefit to improve the symptoms, the optimal treatment of this disease still remains a tough problem. We reported our experience of intravesical hyaluronic acid (HA) and HBO in treating HC and the results seemed interesting. Intravesical HA is easier to do and well tolerated, and it showed a sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for at least 12 months. We suggest it as an alternative and potential way in treating HC.

OBJECTIVE

• ? To compare the efficacy of intravesical hyaluronic acid (HA) instillation and hyperbaric oxygen (HBO) in the treatment of radiation‐induced haemorrhagic cystitis (HC).

PATIENTS AND METHODS

• ? In total 36 patients who underwent radiotherapy for their pelvic malignancies and subsequently suffered from HC were randomly divided into an HA group and an HBO group.
• ? Symptoms of haematuria, frequency of voiding and the visual analogue scale of pelvic pain (range 0–10) were evaluated before and after the treatment with follow‐up of 18 months.

RESULTS

• ? All patients completed this study and no obvious side effects of intravesical HA were recorded.
• ? The improvement rate showed no statistical difference between the two groups at 6, 12 and 18 months after treatment.
• ? Decrease of frequency was significant in both groups 6 months after treatment, but was only significant in the HA group 12 months after therapy.
• ? The improvement in the visual analogue scale remained significant in both groups for 18 months.

CONCLUSIONS

• ? Intravesical instillation of HA was as effective in treating radiation‐induced HC as HBO.
• ? It is well tolerated and resulted in a sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for at least 12 months.

     

Low-dose cyclophosphamide associated with hemorrhagic cystitis in a breast cancer patient

Abstract: Hemorrhagic cystitis is a known complication of high‐dose cyclophosphamide treatment, generally occurring at doses greater than 100 g. There are few reports of hemorrhagic cystitis occurring with low‐dose cyclophosphamide therapy, and this complication has not been described in breast cancer patients. We present a case of a patient with stage IIB breast cancer who developed clinical, radiographic, and pathologic evidence of hemorrhagic cystitis after a single 600 mg/m² dose of cyclophosphamide. Three subsequent cycles of cyclophosphamide with the addition of IV hydration and MESNA were given without complication, and the patient’s urologic symptoms resolved. Repeat cystoscopy demonstrated pathologic resolution of the cystitis. We review the literature regarding proposed mechanisms of hemorrhagic cystitis, and discuss the applicability of these hypotheses in our patient.     

Penile cancer: organ‐sparing techniques

• To compare the oncological safety of treating patients with penile cancer with conservative techniques developed to preserve function, cosmesis and psychological well‐being with more radical ablative strategies.

• We conducted an extensive review of the literature of penile‐preserving and ablative techniques and report on the oncological as well as functional outcomes.

• There were no randomised studies comparing penile‐preserving and ablative techniques.
• Most studies consisted of retrospective cohorts.
• The quality of evidence was level 3 at best.

• Cancer‐specific survival is similar in penile‐preserving and ablative approaches for low‐stage disease.
• Penile preservation is better for functional and cosmetic outcomes and should be offered as a primary treatment method in men with low‐stage penile cancer.

     

Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate‐induced changes in rat urinary bladder

What's known on the subject? and What does the study add? The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry.

OBJECTIVE

• ? To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl‐containing leukotrienes, on protamine sulphate (PS)‐induced changes in rat urinary bladder.

MATERIALS AND METHODS

• ? Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h.
• ? In the PS‐applied and ML‐treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days.
• ? The urinary bladder was investigated for general morphology under a light microscope.
• ? Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry.

RESULTS

• ? Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope.
• ? Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions.
• ? In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions.
• ? The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings.

CONCLUSION

• ? Montelukast appears to have a protective function in the bladder injury model via the anti‐inflammatory effects of this leukotriene receptor antagonist.

     

The management of cyclophosphamide‐induced haematuria

Haemorrhagic cystitis is a frequent complication of treatment with cyclophosphamide. It remains a difficult clinical problem to treat, compounded by the frailty of patient. Furthermore, the preventative measures and treatments available for CP‐induced haematuria have their own benefits and disadvantages.     

Bladder botulinum toxin A injection can benefit patients with radiation and chemical cystitis

OBJECTIVE

To investigate the potential utility of botulinum toxin A (BoNT‐A) bladder injections in patients with radiation cystitis and bacillus Calmette‐Guérin (BCG)‐induced chemical cystitis.

PATIENTS AND METHODS

In all, six patients with refractory radiation cystitis were treated with 200 U bladder BoNT‐A injections and two patients with refractory cystitis after intravesical BCG therapy were treated with 100 U bladder BoNT‐A injections. All the patients were refractory to anticholinergic agents. Under sedation or local anaesthesia, BoNT‐A was injected through a cystoscope into 20 sites submucosally in the trigone and floor of the bladder.

RESULTS

There were no side‐effects or retention after BoNT‐A injection. In five of the six patients with radiation cystitis there was a moderate to significant improvement; the mean (sd ) bladder capacity increased from 105 (25) mL to 250 (35) mL and the urinary frequency decreased from 14 (2) to 11 (1) episodes per day. In the two patients with BCG cystitis both reported significant symptomatic improvement; the mean (sd ) bladder capacity increased from 110 (23) to 230 (23) mL, the urinary frequency decreased from 16 (1) to 12 (1) episodes per day, and using a 10‐point visual analogue pain scoring system, the perceived pain score decreased from 8 to 2. Microscopically, the bladder tissue at 1 month after BCG injection showed marked acute and chronic inflammation with eosinophilic infiltration and focal granulomatous formation. At 2 months after BoNT‐A injection, there was only a mild degree of chronic inflammation with few eosinophils.

CONCLUSION

These preliminary results suggest that BoNT‐A injected into the bladder is a promising treatment for patients with refractory radiation and BCG cystitis.     

Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions

What's known on the subject? and What does the study add? Nearly 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of dietary comestibles. Current questionnaire‐based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. At present we recommend employing a controlled method to determine dietary sensitivities, such as an elimination diet, in order to identify sensitivities while at the same time maintain optimal nutritional intake. We review current literature with regard to diet's effect upon IC/BPS and common comorbidities (irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, neuropathic pain, vulvodynia, and headache) with a focus upon questionnaire‐based investigations. We discuss the pathologic mechanisms that may link diet and IC/BPS related‐pain, concentrating upon specific comestibles such as acidic foods, foods high in potassium, caffeine, and alcohol.

• ? Up to 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of comestibles.
• ? Pathological mechanisms suggested to be responsible for the relationship between dietary intake and symptom exacerbation include peripheral and/or central neural upregulation, bladder epithelial dysfunction, and organ ‘cross‐talk’, amongst others.
• ? Current questionnaire‐based data suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms.
• ? Specific comestible sensitivities varied between patients and may have been influenced by comorbid conditions.
• ? This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management.

     

Combined 18F‐fluorocholine and 18F‐fluoride positron emission tomography/computed tomography imaging for staging of high‐risk prostate cancer

Study Type – Diagnosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Positron emission tomography/computed tomography (PET/CT) with choline and fluoride for the detection of metastases in patients with prostate cancer have each been evaluated, with mixed results. Choline PET/CT has been evaluated against pelvic lymphadenectomy, generally with a low sensitivity but a high specificity; however, the study populations have been heterogenous. Fluoride PET/CT has been evaluated against other imaging methods, such as bone scan, single photon emission CT and MRI, and has been shown to have high specificity as well as sensitivity for bone metastases, but there are no studies with biopsy verification. This is the first study that evaluates the clinical use of both choline and fluoride PET/CT on the same patients in a well‐defined population of patients with high‐risk prostate cancer.

OBJECTIVE

• ? To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both ¹⁸F‐fluorocholine and ¹⁸F‐fluoride as markers, add clinically relevant information for patients with prostate cancer who have high‐risk tumours and a normal or inconclusive planar bone scan.

PATIENTS AND METHODS

• ? Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8–10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a ¹⁸F‐fluorocholine and a ¹⁸F‐fluoride PET/CT.
• ? None of the patients received hormonal therapy before the staging procedures were completed.

RESULTS

• ? For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases.
• ? ¹⁸F‐fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%).
• ? ¹⁸F‐fluoride PET/CT was suggestive for bone metastases in 37 patients (41%).
• ? In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non‐curative.
• ? Of the patients with positive scans, 74% had Gleason score 8–10 tumours. Of the patients with Gleason score 8–10 tumours, 64% had positive scans.

CONCLUSIONS

• ? PET/CT scans with ¹⁸F‐fluorocholine and ¹⁸F‐fluoride commonly detect metastases in patients with high‐risk prostate cancer and a negative or inconclusive bone scan.
• ? For 20% of the patients the results of the PET/CT scans changed the treatment plan.

     

Mechanisms and urodynamic effects of a potent and selective EP4 receptor antagonist,MF191, on cyclophosphamide and prostaglandin E2‐induced bladder overactivity in rats

Study Type – Aetiology (case control) Level of Evidence 3b What's known on the subject? and What does the study add? Recent evidence has suggested that up‐regulation of the prostaglandin E₂ (PGE₂) receptor subtype 4 (EP4) receptor in the bladder is involved in bladder overactivity. The present study found that MF191, a selective EP4 receptor antagonist, may have effects on the bladder urothelium and inflammatory cells and suppress CYP‐ or PGE₂‐induced bladder overactivity. Systemic or intravesical MF191 administration for the treatment of overactive bladder may merit clinical study.

OBJECTIVE

• ? To investigate the mechanisms and urodynamic effects of a potent and selective prostaglandin E₂ (PGE₂) receptor subtype 4 (EP4) antagonist, MF191, on cyclophosphamide (CYP) or PGE₂‐induced bladder overactivity in rats.

MATERIALS AND METHODS

• ? Experimental and control rats were injected with CYP (200 mg/kg i.p.) or saline on day 1. Continuous cystometrogram (CMGs) were performed on day 3.
• ? In group 1, MF191 (vehicle 0.1 and 1 mg/kg) was given i.v. The bladder was then harvested for histology and immunohistochemistry. Some bladders were harvested for analysis of EP4 expression by Western blotting without a CMG study.
• ? In group 2, MF191 (vehicle 10 nM, and 100 nM) was continuously infused into the bladder.
• ? In group 3, bladder overactivity was induced by intravesical instillation of PGE₂ (200 uM) and vehicle or MF191 (1 mg/kg) was given i.v.

RESULTS

• ? CYP induced bladder inflammation, overactivity and EP4 upregulation. The CYP effects were suppressed by MF191 (1 mg/kg i.v.; intercontraction interval [ICI]: 39.4% increase, and reduced inflammatory cells infiltration, and EP4 expression).
• ? Intravesical instillation of MF191 (100 nM) suppressed CYP‐induced bladder overactivity (ICI: 71.8% increase).
• ? PGE₂‐induced bladder overactivity was suppressed by MF191 (ICI: 43.2% increase).
• ? MF191 had no significant effects on other CMG variables or on control rats.

CONCLUSIONS

• ? MF191 might affect the bladder urothelium and inflammatory cells and suppresses CYP‐ or PGE₂‐induced bladder overactivity.
• ? Systemic or intravesical MF191 administration for the treatment of overactive bladder merits clinical study.

     

Clomiphene citrate is safe and effective for long‐term management of hypogonadism

Study Type – Therapy (population cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE

• ? To assess the efficacy and safety of long‐term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).

PATIENTS AND METHODS

• ? Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
• ? Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
• ? Comparison was made between baseline and post‐treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
• ? The main outcome measures were predictors of response and long‐term results with long‐term CC therapy in hypogonadal patients.

RESULTS

• ? The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
• ? Follow‐up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
• ? Mean femoral neck and lumbar spine BD scores improved significantly.
• ? ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
• ? No adverse events were reported by any patients.

CONCLUSIONS

• ? Clomiphene citrate is an effective long‐term therapy for HG in appropriate patients.
• ? The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

     

Sexual dysfunction in women with ketamine cystitis: a case-control study

Study Type – Prevalence (case control) Level of Evidence 3a What's known on the subject? and What does the study add? Extreme ketamine abuse not only damages the bladder and results in bladder wall fibrosis, but also causes bladder mucosa ulcers. Women with the presence of LUTs and chronic pelvic pain appear to show an impact on sexual functions. Increasing problems of ketamine‐associated cystitis are being seen in daily clinical practice. The present case–control study investigated clinical symptom severity and sexual dysfunction in women with KC. The present study showed, with the exception of the sexual desire domain of the female sexual function index, that patients with KC scored lower on all domains compared to controls. The prevalence of sexual dysfunction was high in patients with KC.

OBJECTIVE

• ? To conduct a case–control study evaluating clinical symptom severity and sexual dysfunction in women with ketamine cystitis (KC).

PATIENTS AND METHODS

• ? In total, 29 patients with KC and 27 controls completed the symptoms survey.
• ? Participants completed a visual pelvic pain analogue scale, an O'Leary‐Sant Interstitial Cystitis Symptom Index and Problem Index questionnaire, a Female Sexual Function Index, and a short form of the Chinese Health Questionnaire‐12.

RESULTS

• ? Both the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were significantly higher in patients with KC compared to controls (P < 0.001).
• ? The prevalence of sexual dysfunction was high in patients with KC.
• ? There was a difference in total adjusted Female Sexual Function Index scores between the patients with KC and controls: mean (sd ) total Female Sexual Function Index score 17.65 (6.15) for KC cases vs 25.87 (4.16) for controls (P < 0.001).
• ? Except for the sexual desire domain of female sexual dysfunction, patients with KC scored lower on all domains compared to controls.
• ? There was no significant difference between patients with KC and controls with respect to mental health as evaluated by the Chinese Health Questionnaire‐12.

CONCLUSIONS

• ? Sexual dysfunction and KC symptoms severely impacted on quality of life.
• ? Mental health had no significant difference between patients with KC and controls.

     

Gleason 7 prostate cancer treated with low‐dose‐rate brachytherapy: lack of impact of primary Gleason pattern on biochemical failure

What's known on the subject? and What does the study add? There appears to be a clear difference in cancer control outcomes for patients with Gleason scores of 3+4 and those with scores of 4+3 after radical prostatectomy. It has been documented that patients with Gleason 4+3 prostate cancer have higher incidences of non‐organ‐confined disease than those with primary pattern 3. Higher rates of extracapsular extension, seminal vesicle invasion and positive margins have been found to be associated with primary pattern 4 over 3. These higher rates of non‐organ‐confined disease can lead to increased biochemical failure, which, in turn, can lead to higher mortality rates. This study provides information on the prognostic significance of primary Gleason pattern in the brachytherapy management of prostate cancer. Study Type – Prognosis (case series) Level of Evidence 4

OBJECTIVES

• ? To report the biochemical outcomes for Gleason 7 prostate cancer treated with brachytherapy.
• ? To analyse the impact of the primary Gleason pattern as well as other disease‐ and treatment‐related factors on outcome.

PATIENTS AND METHODS

• ? A total of 560 patients with Gleason 7 prostate cancer were treated between 1990 and 2008 with brachytherapy, alone or in combination with hormonal therapy and/or external beam radiation therapy.
• ? There were 352 patients with Gleason pattern 3+4 and 208 with Gleason pattern 4+3.
• ? The mean (range) presenting PSA level was 11.2 (1–300) ng/mL, and the median was 7.8 ng/mL.
• ? The presenting clinical stages were T1b in 1%, T1c in 33%, T2a in 16%, T2b in 32%, T2c in 16% and T3 in 2% of patients.

RESULTS

• ? The actuarial freedom from biochemical failure rate at 10 years was 82%.
• ? There was no significant difference between 10‐year freedom from biochemical failure rates for patients with Gleason scores of 3+4 (79%) and those with scores of 4+3 (82%).
• ? Biologically effective dose and presenting PSA level were both significant predictors of biochemical failure in multivariate analysis.

CONCLUSIONS

• ? The primary Gleason pattern in Gleason 7 prostate cancer shows no significant effect on biochemical failure when treated with brachytherapy.
• ? These results are different from those found after radical prostatectomy and are probably attributable to the enhanced local control afforded by a brachytherapy approach to this disease subset.

     

Surgical management for upper urinary tract transitional cell carcinoma (UUT‐TCC): a systematic review

What's known on the subject? and What does the study add? Upper urinary tract transitional cell carcinoma (UUT‐TCC) is an aggressive disease. The mainstay in the treatment of UUT‐TCC is surgical intervention, with oncological control the primary objective. UUT‐TCCs have been conventionally treated with radical nephroureterectomy (NU). This procedure involves removal of the kidney, ureter and ipsilateral excision of a bladder cuff. Whilst open NU has traditionally been the approach used, laparoscopic NU (LNU) is now an increasingly popular and established approach for UUT‐TCC. It is argued that LNU reduces postoperative morbidity without compromising oncological efficacy. With technological evolution, robotic NU has now been attempted in some centres as well. In addition, several techniques have been described to manage the bladder cuff with no agreement as to the most efficacious approach. In a further attempt to reduce morbidity and safeguard nephrons, there have been advocates of a number of nephron‐sparing techniques, e.g. ureteroscopic management, percutaneous approaches, and distal ureterectomy. These approaches obviously raise concern on oncological efficacy with requirement for more stringent long‐term surveillance protocols. This study comprehensively reviews and summarises the evidence comparing various surgical techniques in the management of UUT‐TCC. The review additionally evaluates and critically appraises the quality of evidence available, which currently informs practice.

• ? Surgical management of upper urinary tract transitional cell carcinoma (UUT‐TCC) has significantly changed over the past two decades. Data for several new surgical techniques, including nephron‐sparing surgery (NSS), is emerging.
• ? The study systematically reviewed the literature comparing (randomised and observational studies) surgical and oncological outcomes for various surgical techniques
• ? MEDLINE, EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed were searched to identify suitable studies. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team.
• ? The data analysis was performed using the Cochrane software Review manager version 5. Comparable data from each study was combined in a meta‐analysis where possible. For dichotomous data, odds ratios with 95% confidence intervals (CIs) were estimated based on the fixed‐effects model and according to an intention‐to‐treat analysis. If the data available were deemed not suitable for a meta‐analysis it was described in a narrative fashion.
• ? One randomised control trial (RCT) and 19 observational studies comparing open nephroureterectomy (ONU) and laparoscopic NU (LNU) were identified. The RCT reported the LNU group to have statistically significantly less blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge (2.30 vs 3.65 days, P < 0.001) than the ONU group. At a median follow‐up of 44 months, the overall 5‐year cancer‐specific survival (CSS; 89.9 vs 79.8%) and 5‐year metastasis‐free survival rates (77.4 vs 72.5%) for the ONU were better than for LNU, respectively, although not statistically significant.
• ? A meta‐analysis of the observational studies favoured LNU group for lower urinary recurrence (P < 0.001) and distant metastasis. The meta‐analyses for local recurrence for the two groups were comparable.
• ? One retrospective study comparing ONU with a percutaneous approach for grade 2 disease reported no significant differences in CSS rates (53.8 vs 53.3 months).
• ? Three retrospective studies compared NSS and radical NU, and reported no significant differences in overall CSS and recurrence‐free survival between the two approaches.
• ? Five retrospective studies compared various techniques of en bloc excision of the lower ureter. No technique was reported to be better (operative and oncological) than any other.
• ? This review concludes that there is a paucity of good quality evidence for the various surgical approaches for UUT‐TCC. The techniques have been assessed and reported in many retrospective single‐centre studies favouring LNU for better perioperative outcomes and comparable oncological safety. The reported observational studies data is further supported by one RCT.

     

Single application of high‐intensity focused ultrasound as a first‐line therapy for clinically localized prostate cancer: 5‐year outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐intensity focused ultrasound (HIFU) therapy has been proposed for the treatment of localized prostate cancer (PCa) for all risk levels of tumour recurrence. The study adds data on the efficacy of a single HIFU application in the treatment of PCa with different risks of recurrence. Durable cancer control was achieved in 81.7% of patients with low‐risk disease, with rates of efficacy declining in intermediate‐ and high‐risk tumours. The data suggest that the principal domain for minimal invasive HIFU should be low‐risk disease.

OBJECTIVE

• ? To report cancer control results after a single application of high‐intensity focused ultrasonography (HIFU) in patients with localized prostate cancer (PCa), stratified by tumour recurrence risk according to D'Amico risk classification.

PATIENTS AND METHODS

• ? In a retrospective single‐centre study, we analysed the outcomes of patients with localized PCa who were treated with curative intent between December 2002 and October 2006 using an Ablatherm HIFU device (EDAP‐TMS, France).
• ? Transurethral resection of the prostate or adenomectomy were performed before HIFU to downsize large prostate glands.
• ? Oncological failure was determined by the occurrence of biochemical relapse, positive biopsy and/or metastasis. Biochemical relapse was defined as a PSA nadir +1.2 ng/mL (Stuttgart definition), or as a rise in PSA level to ≥0.5 ng/mL if PSA doubling time was ≤6 months. Kaplan–Meier analysis was performed for survival estimates.

RESULTS

• ? A total of 191 consecutive patients were included in the study. The median (range) patient age was 69.7 (51–82) years, and 38, 34 and 28% of these patients were in the low‐, intermediate‐ and high‐risk groups, respectively.
• ? The median (range) follow‐up was 52.8 (0.2–79.8) months.
• ? At 5 years, overall and cancer‐specific survival rates were 86.3% and 98.4%, respectively.
• ? Stratified by risk group, negative biopsy rates were 84.2%, 63.6%, and 67.5% (P = 0.032), 5‐year biochemical‐free survival rates were 84.8%, 64.9% and 54.9% (P < 0.01), and 5‐year disease‐free survival rates were 81.7%, 53.2% and 51.2% (P < 0.01), respectively.

CONCLUSION

• ? Single‐session HIFU is recommended as a curative approach in elderly patients with low‐risk PCa. Patients at higher risk of tumour progression should be counselled regarding the likely need for salvage therapy, including repeat HIFU.

     

Long‐term endoscopic management of upper tract urothelial carcinoma: 20‐year single‐centre experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Endoscopic management of small, low‐grade, non‐invasive upper tract urothelial cell carcinoma (UTUC) is a management option for selected groups of patients. However, the long‐term survival outcomes of endoscopically‐managed UTUC are uncertain because only four institutions have reported outcomes of more than 40 patients beyond 50 months of follow‐up. Moreover, there is significant variance in the degree of underlying UTUC pathology verification in some of these reports, which precludes an analysis of disease‐specific survival outcomes. The present study represents one of the largest endoscopically managed series of patients with UTUC, with a long‐term follow‐up. The degree of verification of underlying UTUC pathology is one of the highest, which allows a grade‐stratified analysis of different outcomes, including upper‐tract recurrence‐free survival, intravesical recurrence‐free survival, renal unit survival and disease‐specific survival. These outcomes provide further evidence suggesting that endoscopic management of highly selected, low‐grade UTUC can provide effective oncological control, as well as renal preservation, in experienced centres.

OBJECTIVE

• ? To report the long‐term outcomes of patients with upper tract urothelial cell carcinoma (UTUC) who were treated endoscopically (either via ureteroscopic ablation or percutaneous resection) at a single institution over a 20‐year period.

PATIENTS AND METHODS

• ? Departmental operation records were reviewed to identify patients who underwent endoscopic management of UTUC as their primary treatment.
• ? Outcomes were obtained via retrospective analysis of notes, electronic records and registry data.
• ? Survival outcomes, including overall survival (OS), UTUC‐specific survival (disease‐specific survival; DSS), upper‐tract recurrence‐free survival, intravesical recurrence‐free survival, renal unit survival and progression‐free survival, were estimated using Kaplan–Meier methods and grade‐stratified differences were analyzed using the log‐rank test.

RESULTS

• ? Between January 1991 and April 2011, 73 patients underwent endoscopic management of UTUC with a median age at diagnosis of 67.7 years.
• ? All patients underwent ureteroscopy and biopsy‐confirmation of pathology was obtained in 81% (n= 59) of the patients. In total, 14% (n= 10) of the patients underwent percutaneous resection.
• ? Median (range; mean) follow‐up was 54 (1–223; 62.8) months.
• ? Upper tract recurrence occurred in 68% (n= 50). Eventually, 19% (n= 14) of the patients proceeded to nephroureterectomy.
• ? The estimated OS and DSS were 69.7% and 88.9%, respectively, at 5 years, and 40.3% and 77.4%, respectively, at 10 years. The estimated mean and median OS times were 119 months and 107 months, respectively. The estimated mean DSS time was 190 months.

CONCLUSIONS

• ? The present study represents one of the largest reported series of endoscopically‐managed UTUC, with high pathological verification and long‐term follow‐up.
• ? Upper‐tract recurrence is common, which mandates regular ureteroscopic surveillance.
• ? However, in selected patients, this approach has a favourable DSS, with a relatively low nephroureterectomy rate, and therefore provides oncological control and renal preservation in patients more likely to die eventually from other causes.

     

Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase‐2 inhibitor

Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non‐steroidal anti‐inflammatory drugs, anti‐allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase‐2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase‐2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase‐2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.     

Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment

Study Type – Therapy (case series)
Level of Evidence 4 What's known on the subject? and What does the study add? Intravesical BCG treatment has been used worldwide for many decades but there are only a few published reports on persisting BCG infection of the urinary bladder. This is the first report on large tuberculosis‐like ulcers of the urinary bladder after intravesical BCG treatment. The finding results in a recommendation to take urine cultures for mycobacteriae in patients with unclear inflammatory lesions in the bladder after instillation of BCG.

OBJECTIVE

• ? To report a late bacille Calmette–Guérin (BCG) complication previously not described in the literature.

PATIENTS AND METHODS

• ? We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous‐like bladder ulcer.

RESULTS

• ? All patients had high‐grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10–50 mm in diameter, was seen at routine follow‐up cystoscopy 2–34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG‐RIVM than with BCG‐Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3–34 months (median 14 months) after the last instillation.
• ? So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour‐free 15–66 months (median 44 months) after the last transurethral resection before BCG treatment.
• ? Another three patients had one to two non‐invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design.

CONCLUSIONS

• ? This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good.
• ? Mycobacterial cultures of the urine should be performed in BCG‐patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity.
• ? Large studies are warranted to study differences in efficacy and side‐effects between different BCG strains.

     

The prevalence and natural history of urinary symptoms among recreational ketamine users

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Case series have described lower urinary tract symptoms associated with ketamine use including severe pain, frequency, haematuria and dysuria. Little is known regarding the frequency of symptoms, relationship of symptoms with dose and frequency of use and natural history of symptoms once the ketamine user has stopped. This study describes the prevalence of ketamine use in a population of recreational drug users in a dance music setting. It shows a dose–frequency relationship with ketamine use. It shows that urinary symptoms associated with recreational ketamine use may lead to a considerable demand on health resources in the primary‐, secondary‐ and emergency‐care settings. It shows that symptoms may improve once ketamine use is decreased.

OBJECTIVE

• ? To investigate the prevalence and natural history of urinary symptoms in a cohort of recreational ketamine users.

PATIENTS AND METHODS

• ? A purposeful sampling technique was used.
• ? Between November 2009 and January 2010 participants were invited to undertake an on‐line questionnaire promoted by a national dance music magazine and website.
• ? Data regarding demographics and illicit drug‐use were collected.
• ? Among respondents reporting recent ketamine use, additional information detailing their ketamine use, experience of urinary symptoms and use of related healthcare services was obtained.

RESULTS

• ? In all, 3806 surveys were completed, of which 1285 (33.8%) participants reported ketamine use within the last year.
• ? Of the ketamine users, 17% were found to be dependent on the drug; 26.6% (340) of recent ketamine users reported experiencing urinary symptoms.
• ? Urinary symptoms were significantly related to both dose of ketamine used and frequency of ketamine use.
• ? Of 251 users reporting their experience of symptoms over time in relationship to their use of ketamine, 51% reported improvement in urinary symptoms upon cessation of use with only eight (3.8%) reporting deterioration after stopping use.

CONCLUSIONS

• ? Urinary tract symptoms are reported in over a quarter of regular ketamine users.
• ? A dose and frequency response relationship has been shown between ketamine use and urinary symptoms.
• ? Both users and primary‐care providers need to be educated about urinary symptoms that may arise in ketamine users. A multi‐disciplinary approach promoting harm reduction, cessation and early referral is needed to manage individuals with ketamine‐associated urinary tract symptoms to avoid progression to severe and irreversible urological pathologies.

     

Population‐based comparative effectiveness of nephron‐sparing surgery vs ablation for small renal masses

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Case series of patients undergoing various forms of ablation show that it is technically feasible and possible for ablation to achieve short‐ and intermediate‐term cancer‐specific survival rates similar to those of controls undergoing partial nephrectomy. This is the first well‐powered study with a controlled design to compare effectiveness between partial nephrectomy and ablation.

OBJECTIVE

• ? To determine, in a population‐based cohort, if disease‐specific survival (DSS) was equivalent in patients undergoing ablation vs nephron‐sparing surgery (NSS) for clinical stage T1a renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? A retrospective cohort study was performed using patients from the Surveillance, Epidemiology and End Results cancer registry with RCC < 4 cm and no evidence of distant metastases, who underwent ablation or NSS.
• ? Kaplan–Meier and Cox regression analyses were performed to determine if treatment type was independently associated with DSS.

RESULTS

• ? Between 1998 and 2007, a total of 8818 incident cases of RCC were treated with either NSS (7704) or ablation (1114).
• ? The median (interquartile range) follow‐up was 2.8 (1.2–4.7) years in the NSS group and 1.6 (0.7–2.9) years in the ablation group, although 10% of each cohort were followed up beyond 5 years.
• ? After multivariable adjustment, ablation was associated with a twofold greater risk of kidney cancer death than NSS (hazard ratio 1.9, 95% confidence interval 1.1–3.3, P= 0.02).
• ? Age, gender, marital status and tumour size were also significantly associated with outcome.
• ? The predicted probability of DSS at 5 years was 98.3% with NSS and 96.6% with ablation.

CONCLUSION

• ? After controlling for age, gender, marital status and tumour size, the typical patient presenting with clinical stage T1a RCC, who undergoes ablation rather than NSS, has a twofold increase in the risk of kidney cancer death; however, at 5 years the absolute difference is small, and may only be realized by patients with long life expectancies.